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Protein

Mitogen-activated protein kinase kinase kinase 3

Gene

Map3k3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Enzyme regulationi

Activated by phosphorylation on Thr-530.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei391 – 3911ATPPROSITE-ProRule annotation
Active sitei489 – 4891Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi368 – 3769ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. MAP kinase kinase activity Source: GO_Central
  3. MAP kinase kinase kinase activity Source: UniProtKB-EC
  4. metal ion binding Source: UniProtKB-KW
  5. protein kinase activity Source: MGI

GO - Biological processi

  1. activation of MAPK activity Source: GO_Central
  2. blood vessel development Source: MGI
  3. intracellular signal transduction Source: MGI
  4. MAPK cascade Source: GOC
  5. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  6. positive regulation of p38MAPK cascade Source: MGI
  7. protein autophosphorylation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.2. 3474.
ReactomeiREACT_337033. Interleukin-1 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase kinase kinase 3 (EC:2.7.11.25)
Alternative name(s):
MAPK/ERK kinase kinase 3
Short name:
MEK kinase 3
Short name:
MEKK 3
Gene namesi
Name:Map3k3
Synonyms:Mekk3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1346874. Map3k3.

Subcellular locationi

GO - Cellular componenti

  1. intracellular Source: GO_Central
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 626626Mitogen-activated protein kinase kinase kinase 3PRO_0000086246Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei166 – 1661Phosphoserine; by SGK1By similarity
Modified residuei250 – 2501PhosphoserineBy similarity
Modified residuei337 – 3371Phosphoserine; by SGK11 Publication
Modified residuei340 – 3401Phosphoserine1 Publication

Post-translational modificationi

Phosphorylation at Ser-166 and Ser-337 by SGK1 inhibits its activity.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ61084.
PaxDbiQ61084.
PRIDEiQ61084.

PTM databases

PhosphoSiteiQ61084.

Expressioni

Gene expression databases

BgeeiQ61084.
CleanExiMM_MAP3K3.
GenevestigatoriQ61084.

Interactioni

Subunit structurei

Binds both upstream activators and downstream substrates in multimolecular complexes. Part of a complex with MAP2K3, RAC1 and CCM2. Interacts with MAP2K5 and SPAG9.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Map2k5Q9WVS715EBI-446250,EBI-446144
Traf6P701965EBI-446250,EBI-448028

Protein-protein interaction databases

BioGridi204959. 1 interaction.
IntActiQ61084. 4 interactions.
MINTiMINT-1531397.

Structurei

3D structure databases

ProteinModelPortaliQ61084.
SMRiQ61084. Positions 42-126, 336-624.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini44 – 12380PB1PROSITE-ProRule annotationAdd
BLAST
Domaini362 – 622261Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 PB1 domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119077.
HOGENOMiHOG000049130.
HOVERGENiHBG006303.
InParanoidiQ61084.
KOiK04421.
OMAiQALHSIM.
OrthoDBiEOG747PHJ.
PhylomeDBiQ61084.
TreeFamiTF105113.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000270. OPR_PB1.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00666. PB1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q61084-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDEQEALDSI MKDLVALQMS RRTRLSGYET MKNKDTGHPN RQSDVRIKFE
60 70 80 90 100
HNGERRIIAF SRPVRYEDVE HKVTTVFGQP LDLHYMNNEL SILLKNQDDL
110 120 130 140 150
DKAIDILDRS SSMKSLRILL LSQDRNHTSS SPHSGVSRQV RIKPSQSAGD
160 170 180 190 200
INTIYQAPEP RSRHLSVSSQ NPGRSSPPPG YVPERQQHIA RQGSYTSINS
210 220 230 240 250
EGEFIPETSE QCMLDPLSSA ENSLSGSCQS LDRSADSPSF RKSQMSRARS
260 270 280 290 300
FPDNRKECSD RETQLYDKGV KGGTYPRRYH VSVHHKDYND GRRTFPRIRR
310 320 330 340 350
HQGNLFTLVP SSRSLSTNGE NMGVAVQYLD PRGRLRSADS ENALTVQERN
360 370 380 390 400
VPTKSPSAPI NWRRGKLLGQ GAFGRVYLCY DVDTGRELAS KQVQFDPDSP
410 420 430 440 450
ETSKEVSALE CEIQLLKNLQ HERIVQYYGC LRDRAEKILT IFMEYMPGGS
460 470 480 490 500
VKDQLKAYGA LTESVTRKYT RQILEGMSYL HSNMIVHRDI KGANILRDSA
510 520 530 540 550
GNVKLGDFGA SKRLQTICMS GTGIRSVTGT PYWMSPEVIS GEGYGRKADV
560 570 580 590 600
WSLGCTVVEM LTEKPPWAEY EAMAAIFKIA TQPTNPQLPS HISEHGRDFL
610 620
RRIFVEARQR PSAEELLTHH FAQLVY
Length:626
Mass (Da):70,776
Last modified:November 1, 1996 - v1
Checksum:i00EF2442C9E56E0B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43187 mRNA. Translation: AAB03535.1.
BC023781 mRNA. Translation: AAH23781.1.
CCDSiCCDS25548.1.
RefSeqiNP_036077.1. NM_011947.3.
UniGeneiMm.27041.

Genome annotation databases

EnsembliENSMUST00000002044; ENSMUSP00000002044; ENSMUSG00000020700.
GeneIDi26406.
KEGGimmu:26406.
UCSCiuc007lyc.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43187 mRNA. Translation: AAB03535.1.
BC023781 mRNA. Translation: AAH23781.1.
CCDSiCCDS25548.1.
RefSeqiNP_036077.1. NM_011947.3.
UniGeneiMm.27041.

3D structure databases

ProteinModelPortaliQ61084.
SMRiQ61084. Positions 42-126, 336-624.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204959. 1 interaction.
IntActiQ61084. 4 interactions.
MINTiMINT-1531397.

PTM databases

PhosphoSiteiQ61084.

Proteomic databases

MaxQBiQ61084.
PaxDbiQ61084.
PRIDEiQ61084.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000002044; ENSMUSP00000002044; ENSMUSG00000020700.
GeneIDi26406.
KEGGimmu:26406.
UCSCiuc007lyc.1. mouse.

Organism-specific databases

CTDi4215.
MGIiMGI:1346874. Map3k3.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119077.
HOGENOMiHOG000049130.
HOVERGENiHBG006303.
InParanoidiQ61084.
KOiK04421.
OMAiQALHSIM.
OrthoDBiEOG747PHJ.
PhylomeDBiQ61084.
TreeFamiTF105113.

Enzyme and pathway databases

BRENDAi2.7.12.2. 3474.
ReactomeiREACT_337033. Interleukin-1 signaling.

Miscellaneous databases

ChiTaRSiMap3k3. mouse.
NextBioi304381.
PROiQ61084.
SOURCEiSearch...

Gene expression databases

BgeeiQ61084.
CleanExiMM_MAP3K3.
GenevestigatoriQ61084.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000270. OPR_PB1.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00666. PB1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of mitogen-activated protein/ERK kinase kinases (MEKK) 2 and 3. Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase."
    Blank J.L., Gerwins P., Elliott E.M., Sather S., Johnson G.L.
    J. Biol. Chem. 271:5361-5368(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
    Tissue: Brain.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Mammary gland.
  3. "JLP: a scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors."
    Lee C.M., Onesime D., Reddy C.D., Dhanasekaran N., Reddy E.P.
    Proc. Natl. Acad. Sci. U.S.A. 99:14189-14194(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SPAG9.
  4. Cited for: INTERACTION WITH MAP2K3; RAC1 AND CCM2.
  5. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-337 AND SER-340, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiM3K3_MOUSE
AccessioniPrimary (citable) accession number: Q61084
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: April 1, 2015
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.